TECOS 2013.

Methods	Study design: parallel RCT Study time frame: December 2008 to July 2012 Duration of follow‐up: median follow‐up 3.0 years
Participants	Country: 38 countries (Europe, North and South America, Asia, Oceania and Israel) Setting: multicentre (673 sites) Inclusion criteria: Type 2 DM with established CVD, defined as a history of major coronary artery disease, ischaemic cerebrovascular disease, or atherosclerotic peripheral arterial disease; at least 50 years of age; HbA1c of 6.5 to 8.0% when treated with stable doses of one or two oral antihyperglycaemic agents (metformin, pioglitazone, or sulphonylureas) or insulin (with or without metformin) Number: treatment group (); control group () eGFR < 60 mL/min/1.73m2: treatment group (1667); control group (1657) Mean age ± SD: 68.8 ± 7.9 years (not reported for groups) Sex (M/F): 2060/1263 (not reported for groups) Exclusion criteria: taken a DPP‐4 inhibitor, glucagon‐like peptide‐1 receptor agonist, or thiazolidinedione (other than pioglitazone) during the preceding 3 months; history of two or more episodes of severe hypoglycaemia (defined as requiring third party assistance) during the preceding 12 months; eGFR < 30 mL/min/1.73 m2 at baseline
Interventions	Treatment group Sitagliptin: 100 mg/d (or 50 mg/d if the baseline eGFR was ≥ 30 and < 50 mL/min/1.73 m2) Control group Placebo
Outcomes	Composite cardiovascular outcome" defined as the first confirmed event of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalisation for unstable angina The secondary composite cardiovascular outcome was the first confirmed event of cardiovascular death, nonfatal MI, or nonfatal stroke. Other secondary outcomes included the occurrence of the individual components of the primary composite cardiovascular outcome, fatal and nonfatal MI, fatal and nonfatal stroke, death from any cause, and hospitalisation for heart failure Changes in the glycated haemoglobin level and the eGFR, initiation of additional antihyperglycaemic agents or long‐term insulin therapy, and frequency of severe hypoglycaemia, adverse events, severe hypoglycaemia, and expected diabetes‐related complications.
Notes	Written to authors for further data for the subgroup analysis for those patients with an eGFR < 60. Authors reported that data not available currently as they will publish the subgroup analysis. Funding source: Merck
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"An interactive voice‐response system assigned the study medication in a double‐blind manner, blocked within each site"
Allocation concealment (selection bias)	Low risk	"An interactive voice‐response system assigned the study medication in a double‐blind manner, blocked within each site"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"An interactive voice‐response system assigned the study medication in a double‐blind manner, blocked within each site"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"A clinical events committee (CEC), blinded to treatment allocation and independent of the sponsor, will adjudicate events including cardiovascular‐related death, non‐fatal MI, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure requiring hospitalization, and acute pancreatitis"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low rate of discontinuation for the whole population (not just eGFR < 60) in both sitagliptin arm (360/7332; 4.9%) and placebo arm (434/7339; 5.9%)
Selective reporting (reporting bias)	Low risk	The prespecified outcomes were available on a clinical trials database and all major outcomes were reported
Other bias	High risk	Conflicts of interest: The study was supported by Merck, the manufacturer of sitagliptin. All authors except 2, either received research grants, consulting fees, travel reimbursements and/or speaker fees from Merck or were employees of Merck with shares in the company